Th17 cell and inflammatory cytokine (IL-17A, IL-17F, etc.) produced thereby has been drawing attention, since they cause a decrease in QOL as a severe etiology cell and factor accompanying enhancement of a systemic new immune response, in various autoimmune disease such as inflammatory bowel disease (IBD), rheumatoid arthritis, multiple sclerosis or psoriasis. However, the existing therapeutic drugs show only limited effects, and therefore, the earliest possible development of a novel therapeutic drug has been desired.
Moreover, it has been recently clarified that a Retinoid-related Orphan Receptor (ROR) γt, which is one of the orphan nuclear receptors, plays an important role in the differentiation of Th17 cells and production of IL-17A/IL-17F. That is, it has been reported that RORγt is mainly expressed in Th17 cells and functions as a transcription factor of IL-17A and IL-17F, as well as a master regulator of Th17 cell differentiation.
Therefore, a medicament that inhibits the action of RORγt is expected to show a treatment effect on various immune disease by suppressing differentiation and activation of Th17 cells.
Patent Document 1 reports the following compound represented by the general formula:P-M-M1 wherein    M is a 3- to 8-membered linear chain consisting of carbon atoms, 0-3 carbonyl groups, 0-1 thiocarbonyl group, and 0-4 heteroatoms selected from O, N and S(O)p,    one of P and M1 is -G, and the other is -A-B;    G is a group represented by the formula (IIa) or formula (IIb):
    Ring D, including the two atoms of Ring E to which it is attached, is a 5- or 6-membered ring consisting of carbon atoms and 0-3 heteroatoms selected from N, O and S(O)p;    Ring D is substituted with 0-2 R or 0-2 carbonyl, and there are 0-3 ring double bonds;    Ring E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl and pyridazinyl, which is substituted with 1-3 R;    A is selected from a C3-10 carbocycle substituted with 0-2 R4, and a 5- to 12-membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from N, O and S(O)p, and substituted with 0-2 R4;    B is X—Y—R4a or the like;    X is absent, —(CR2R2a)1-4— or the like;    Y is selected from a C3-10 carboncycle and a 3- to 10-membered heterocycle; and    R4a is a C1-6 alkyl substituted with 0-2 R4c, or the like,    which has a Xa factor inhibitory action, and is useful for the treatment of thromboembolism.
Patent Document 2 discloses, as a fused heterocyclic compound, a compound represented by the formula:
wherein    R1A is an optionally substituted hydrocarbon group or an optionally substituted hydrocarbon-oxy group,    R2A and R3A are each independently a hydrogen atom, an optionally substituted hydrocarbon group or the like, or    R2A and R3A in combination optionally form, together with the carbon atoms which they are bonded to, an optionally substituted hydrocarbon ring,    R5A is a hydrogen atom or a halogen atom,    Q′ is
                wherein        [A1] are the same or different and each is a methylene group optionally substituted by C1-6 alkyl group(s) optionally substituted by hydroxy group(s) and the like, wherein the two substituents bonded to the single carbon atom are optionally combined to each other to form a hydrocarbon ring, and        n is an integer of 1 to 5, or the like, and            Ring B′ is a benzene ring optionally further having substituent(s), or the like,    which has a RORγt inhibitory action, and is useful for the treatment of inflammatory bowel disease (IBD) and the like.
Patent Document 3 discloses, as a heterocyclic compound, a compound represented by the formula:
wherein    Ring A is an optionally substituted cyclic group,    Q is a bond, an optionally substituted C1-10 alkylene, an optionally substituted C2-10 alkenylene or an optionally substituted C2-10 alkynylene,    R1 is a substituent,    Ring B is a thiazole ring, an isothiazole ring or a dihydrothiazole ring, each optionally further substituted in addition to R2, and    R2 is an optionally substituted cyclyl-carbonyl-C1-6 alkyl group, an optionally substituted aminocarbonyl-C1-6 alkyl group, an optionally substituted cyclyl-C1-6 alkyl group, an optionally substituted cyclyl-C1-6 alkylamino-carbonyl group, an optionally substituted aminocarbonyl-C2-6 alkenyl group, an optionally substituted C1-6 alkylcarbonylamino-C1-6 alkyl group, an optionally substituted cyclyl-aminocarbonyl group, an optionally substituted cyclyl-carbonyl group or an optionally substituted non-aromatic heterocyclic group,    which has a RORγt inhibitory action, and is useful for the treatment of inflammatory disease, autoimmune disease and the like.
Patent Document 4 discloses, as a heterocyclic compound, a compound represented by the formula:
wherein    Ring A is a C3-10 carbocycle;    L is a group selected from a bond, —CHR10CHR10—, —CR10═CR10— and —C≡C—;    R10 is H, halo, OH or C1-4 alkyl;    Q is selected from C, CH and N;     is an optional bond; provided that when Q is N, then the optional bond is absent;    Ring B is a 5- to 6-membered heterocycle containing heteroatoms selected from N, NR6, O and S(O)p, and substituted by 0-3 R5;    optionally, Ring B is further fused with phenyl substituted with 0-2 R5 or a 5- to 6-membered aromatic heterocycle containing 1 to 2 heteroatoms selected from N, NR6, O and S(O)p, and substituted with 0-2 R5;    R1 are each independently H, halo, C1-2 alkyl, —O(C1-4 alkyl), CN, —CH2NH2 or —C(═NH)NH2;    R2 is H, halo, CN, OH, C1-6 alkyl, C1-4 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, CO(C1-4 alkyl), CONH2, CO2H, and a 5- to 7-membered heterocycle containing 1 to 4 heteroatoms selected from N, NH, N(C1-4 alkyl), O and S(O)p, and substituted with 1-2 R2a; and    R3 is a C1-6 alkyl group substituted with 1-3 R3a, a C3-10 carboncycle substituted with 1-3 R3, or a 5- to 10-membered heterocycle containing 1 to 4 heteroatoms selected from N, NR7, O and S(O)p, and substituted with 1-3 R3a,    which is a Factor XIIa, and is useful for the treatment of thromboembolism, inflammatory disease and the like.
Patent Document 5 discloses, as a heterocyclic compound, a compound represented by the formula:
wherein    A1 is CRA1 wherein RA1 is a hydrogen atom or a substituent, or a nitrogen atom,    A2 is CRA2 wherein RA2 is a hydrogen atom or a substituent, or a nitrogen atom,    A3 is CRA3 wherein RA3 is a hydrogen atom or a substituent, or a nitrogen atom, or,    provided that when A2 is CRA2 wherein RA2 is a substituent, and    A3 is CRA3 wherein RA3 is a substituent, then RA2 and RA3 in combination optionally form, together with the carbon atoms which they are bonded to, a carbocycle or a heterocycle,    R1 is 1) an optionally substituted carbocyclic group, 2) an optionally substituted monocyclic heterocyclic group (excluding an optionally substituted 2-oxo-3-azetidyl group), 3) an optionally substituted fused heterocyclic group (excluding an optionally substituted 7-oxo-4-thia-1-azabicyclo[3.2.0]hept-6-yl group, an optionally substituted 8-oxo-1-azabicyclo[4.2.0]oct-2-en-7-yl group and an optionally substituted 8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl group), or 4) an optionally substituted spiro ring group,    R2 is a hydrogen atom or a substituent,    one of R3 or R4 is an optionally substituted carbocyclic group, an optionally substituted aromatic nitrogen-containing heterocyclic group or an optionally substituted fused non-aromatic heterocyclic group, and the other is a hydrogen atom or a substituent,    R5 is a hydrogen atom or a substituent, and    R9 is a hydrogen atom or a hydroxy group, provided that when R9 is a hydroxy group, then A1, A2 and A3 are CRA1, CRA2 and CRA3, respectively.    which has a RORγt inhibitory action, and is useful for the treatment of inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, multiple sclerosis, psoriasis and the like.
Patent Document 6 discloses, as a heterocyclic compound, a compound represented by the formula:
wherein    R1 is C1-2 alkyl, halogen or CF3;    R2 is H, Cl, F or methyl;    R3 is H, methyl;    R4 is H, C1-6 alkyl or benzyl optionally substituted by CF3;    R5 is methyl, nitro, halogen, CN, CF3 or —C(O)OCH2CH3;    R6 is Cl, F or CF3; and    m is 0 or 1,    which is an androgen receptor modulator.